IL-10 is a key cytokine in psoriasis. Proof of principle by IL-10 therapy: a new therapeutic approach.
Overexpression of proinflammatory, type 1 cytokines has been demonstrated in psoriasis and is believed to be of pathophysiological importance. IL-10 is a type 2 cytokine with major impact on immunoregulation, since it inhibits type 1/proinflammatory cytokine formation. Therefore, we investigated its role in psoriasis. We found a relative deficiency in cutaneous IL-10 mRNA expression compared with other inflammatory dermatoses. Interestingly, patients during established antipsoriatic therapy showed higher IL-10 mRNA expression of peripheral blood mononuclear cells than patients before therapy. This suggested that IL-10 may have antipsoriatic capacity. Therefore, we performed a phase 2 pilot trial with subcutaneous IL-10 administration (8 microg/kg/d) over 24 d in three patients. Clinical efficiency measured by objective and subjective parameters was found. Immunosuppressive effects (depressed monocytic HLA-DR expression, TNF-alpha and IL-12 secretion capacity, IL-12 plasma levels, and responsiveness to recall antigens) as well as a shift toward a type 2 cytokine pattern (increasing proportion of IL-4, IL-5, and IL-10 producing T cells, selective increase in IgE serum levels) were observed. Remarkably, IL-10 administration also enhanced the intracutaneous IL-10 mRNA expression. Our investigations demonstrate the major importance of IL-10 in psoriasis and show that IL-10 administration represents a new therapeutic approach. This is the first report on IL-10 therapy for cutaneous disorders.
Asadullah
K
K
Department of Dermatology, University Hospital Charité, Berlin Humboldt University, D-10098 Berlin, Germany. asadullah@rz.charite.hu-berlin.de
Sterry
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W
Stephanek
K
K
Jasulaitis
D
D
Leupold
M
M
Audring
H
H
Volk
H D
HD
Döcke
W D
WD
D000328:Adult; D006801:Humans; D016753:Interleukin-10 / Q000008:administration & dosage* / Q000096:biosynthesis / Q000172:deficiency / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011565:Psoriasis / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D012333:RNA, Messenger; D016896:Treatment Outcome
D015848:Interleukin-5; D012333:RNA, Messenger; D016753:Interleukin-10; D015847:Interleukin-4